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      Inferring multi-scale neural mechanisms with brain network modelling

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          Abstract

          The neurophysiological processes underlying non-invasive brain activity measurements are incompletely understood. Here, we developed a connectome-based brain network model that integrates individual structural and functional data with neural population dynamics to support multi-scale neurophysiological inference. Simulated populations were linked by structural connectivity and, as a novelty, driven by electroencephalography (EEG) source activity. Simulations not only predicted subjects' individual resting-state functional magnetic resonance imaging (fMRI) time series and spatial network topologies over 20 minutes of activity, but more importantly, they also revealed precise neurophysiological mechanisms that underlie and link six empirical observations from different scales and modalities: (1) resting-state fMRI oscillations, (2) functional connectivity networks, (3) excitation-inhibition balance, (4, 5) inverse relationships between α-rhythms, spike-firing and fMRI on short and long time scales, and (6) fMRI power-law scaling. These findings underscore the potential of this new modelling framework for general inference and integration of neurophysiological knowledge to complement empirical studies.

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          Neuroscientists can use various techniques to measure activity within the brain without opening up the skull. One of the most common is electroencephalography, or EEG for short. A net of electrodes is attached to the scalp and reveals the patterns of electrical activity occurring in brain tissue. But while EEG is good at revealing electrical activity across the surface of the scalp, it is less effective at linking the observed activity to specific locations in the brain.

          Another widely used technique is functional magnetic resonance imaging, or fMRI. A patient, or healthy volunteer, lies inside a scanner containing a large magnet. The scanner tracks changes in the level of oxygen at different regions of the brain to provide a measure of how the activity of these regions changes over time. In contrast to EEG, fMRI is good at pinpointing the location of brain activity, but it is an indirect measure of brain activity as it depends on blood flow and several other factors. In terms of understanding how the brain works, EEG and fMRI thus provide different pieces of the puzzle. But there is no easy way to fit these pieces together.

          Other areas of science have used computer models to merge different sources of data to obtain new insights into complex processes. Schirner et al. now adopt this approach to reveal the workings of the brain that underly signals like EEG and fMRI.

          After recording structural MRI data from healthy volunteers, Schirner et al. built a computer model of each person’s brain. They then ran simulations with each individual model stimulating it with the person’s EEG to predict the fMRI activity of the same individual. Comparing these predictions with real fMRI data collected at the same time as the EEG confirmed that the predictions were accurate. Importantly, the brain models also displayed many features of neural activity that previously could only be measured by implanting electrodes into the brain.

          This new approach provides a way of combining experimental data with theories about how the nervous system works. The resulting models can help generate and test ideas about the mechanisms underlying brain activity. Building models of different brains based on data from individual people could also help reveal the biological basis of differences between individuals. This could in turn provide insights into why some individuals are more vulnerable to certain brain diseases and open up new ways to treat these diseases.

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          Most cited references55

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          Alpha-band oscillations, attention, and controlled access to stored information

          Alpha-band oscillations are the dominant oscillations in the human brain and recent evidence suggests that they have an inhibitory function. Nonetheless, there is little doubt that alpha-band oscillations also play an active role in information processing. In this article, I suggest that alpha-band oscillations have two roles (inhibition and timing) that are closely linked to two fundamental functions of attention (suppression and selection), which enable controlled knowledge access and semantic orientation (the ability to be consciously oriented in time, space, and context). As such, alpha-band oscillations reflect one of the most basic cognitive processes and can also be shown to play a key role in the coalescence of brain activity in different frequencies.
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            EEG alpha and theta oscillations reflect cognitive and memory performance: a review and analysis.

            Evidence is presented that EEG oscillations in the alpha and theta band reflect cognitive and memory performance in particular. Good performance is related to two types of EEG phenomena (i) a tonic increase in alpha but a decrease in theta power, and (ii) a large phasic (event-related) decrease in alpha but increase in theta, depending on the type of memory demands. Because alpha frequency shows large interindividual differences which are related to age and memory performance, this double dissociation between alpha vs. theta and tonic vs. phasic changes can be observed only if fixed frequency bands are abandoned. It is suggested to adjust the frequency windows of alpha and theta for each subject by using individual alpha frequency as an anchor point. Based on this procedure, a consistent interpretation of a variety of findings is made possible. As an example, in a similar way as brain volume does, upper alpha power increases (but theta power decreases) from early childhood to adulthood, whereas the opposite holds true for the late part of the lifespan. Alpha power is lowered and theta power enhanced in subjects with a variety of different neurological disorders. Furthermore, after sustained wakefulness and during the transition from waking to sleeping when the ability to respond to external stimuli ceases, upper alpha power decreases, whereas theta increases. Event-related changes indicate that the extent of upper alpha desynchronization is positively correlated with (semantic) long-term memory performance, whereas theta synchronization is positively correlated with the ability to encode new information. The reviewed findings are interpreted on the basis of brain oscillations. It is suggested that the encoding of new information is reflected by theta oscillations in hippocampo-cortical feedback loops, whereas search and retrieval processes in (semantic) long-term memory are reflected by upper alpha oscillations in thalamo-cortical feedback loops. Copyright 1999 Elsevier Science B.V.
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              Electrophysiological signatures of resting state networks in the human brain.

              Functional neuroimaging and electrophysiological studies have documented a dynamic baseline of intrinsic (not stimulus- or task-evoked) brain activity during resting wakefulness. This baseline is characterized by slow (<0.1 Hz) fluctuations of functional imaging signals that are topographically organized in discrete brain networks, and by much faster (1-80 Hz) electrical oscillations. To investigate the relationship between hemodynamic and electrical oscillations, we have adopted a completely data-driven approach that combines information from simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). Using independent component analysis on the fMRI data, we identified six widely distributed resting state networks. The blood oxygenation level-dependent signal fluctuations associated with each network were correlated with the EEG power variations of delta, theta, alpha, beta, and gamma rhythms. Each functional network was characterized by a specific electrophysiological signature that involved the combination of different brain rhythms. Moreover, the joint EEG/fMRI analysis afforded a finer physiological fractionation of brain networks in the resting human brain. This result supports for the first time in humans the coalescence of several brain rhythms within large-scale brain networks as suggested by biophysical studies.
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                Author and article information

                Contributors
                Role: Reviewing Editor
                Journal
                eLife
                Elife
                eLife
                eLife
                eLife Sciences Publications, Ltd
                2050-084X
                08 January 2018
                2018
                : 7
                : e28927
                Affiliations
                [1 ]Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Neurology BerlinGermany
                [2 ]Berlin Institute of Health (BIH) BerlinGermany
                [3 ]Bernstein Focus State Dependencies of Learning & Bernstein Center for Computational Neuroscience BerlinGermany
                [4 ]deptRotman Research Institute of Baycrest Centre University of Toronto TorontoCanada
                [5 ]Institut de Neurosciences des Systèmes UMR INSERM 1106, Aix-Marseille Université Faculté de Médecine MarseilleFrance
                [6 ]deptCenter for Brain and Cognition, Computational Neuroscience Group, Department of Information and Communication Technologies Universitat Pompeu Fabra BarcelonaSpain
                [7 ]Institució Catalana de la Recerca i Estudis Avançats (ICREA) BarcelonaSpain
                [8 ]deptDepartment of Neuropsychology Max Planck Institute for Human Cognitive and Brain Sciences LeipzigGermany
                [9 ]deptSchool of Psychological Sciences Monash University MelbourneAustralia
                [10 ]deptBerlin School of Mind and Brain & MindBrainBody Institute Humboldt University BerlinGermany
                [11]Columbia University College of Physicians and Surgeons United States
                [12]Columbia University College of Physicians and Surgeons United States
                Author information
                http://orcid.org/0000-0001-8227-8476
                http://orcid.org/0000-0002-8251-8860
                http://orcid.org/0000-0002-4643-4782
                Article
                28927
                10.7554/eLife.28927
                5802851
                29308767
                6a00d08d-6849-4171-9ef5-123dc253d5fd
                © 2018, Schirner et al

                This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

                History
                : 23 May 2017
                : 04 January 2018
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000913, James S. McDonnell Foundation;
                Award ID: Brain Network Recovery Group JSMF22002082
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100007601, Horizon 2020;
                Award ID: Research and Innovation Programme (720270)
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100002347, Bundesministerium für Bildung und Forschung;
                Award ID: Bernstein Focus State Dependencies of Learning 01GQ0971-5
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100007601, Horizon 2020;
                Award ID: ERC Consolidator Grant BrainModes 683049
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100002347, Bundesministerium für Bildung und Forschung;
                Award ID: US-German Collaboration in Computational Neuroscience 01GQ1504A
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100002347, Bundesministerium für Bildung und Forschung;
                Award ID: Max-Planck Society
                Award Recipient :
                Funded by: John von Neumann Institute for Computing at Jülich Supercomputing Centre;
                Award ID: Grant NIC#8344
                Award Recipient :
                Funded by: Stiftung Charité/Private Exzellenzinitiative Johanna Quandt and Berlin Institute of Health;
                Award Recipient :
                Funded by: John von Neumann Institute for Computing at Jülich Supercomputing Centre;
                Award ID: Grant NIC#10276
                Award Recipient :
                The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
                Categories
                Research Article
                Computational and Systems Biology
                Neuroscience
                Custom metadata
                Hybrid brain network models predict neurophysiological processes that link structural and functional empirical data across scales and modalities in order to better understand neural information processing and its relation to brain function.

                Life sciences
                brain modeling,connectomics,resting-state networks,fmri,eeg,alpha rhythm,human
                Life sciences
                brain modeling, connectomics, resting-state networks, fmri, eeg, alpha rhythm, human

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